Karin F. Hoth, Ph.D. - US grants

DESCRIPTION (provided by applicant): Heart failure is one of the most significant causes of hospitalization, morbidity and mortality among elderly individuals in the United States. Research has demonstrated that patients with heart failure show cognitive impairment, which can impact functional abilities and quality of life. Medical interventions including implanted devices have led to improvements in symptom control and slowed progression of disease among patients with heart failure. Cardiac resynchronization therapy (CRT), a recently developed pacemaker based intervention, is associated with improvements on a range of cardiac functioning measures as well as enhanced health status and quality of life. However, no studies have examined cognitive functioning in this population, particularly in the context of change in cardiac functioning before and after CRT. In the present study, cardiac function and cognition will be examined among patients with heart failure before and after cardiac resynchronization therapy. This integration of cardiac and cognitive measures will help to elucidate the mechanisms by which cardiac disease is associated with cognitive decline, and will provide data on the effects of CRT on cognition.

SUMMARY/ABSTRACT Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of morbidity and mortality in the US with increasing prevalence in older adults. The impact of COPD on the brain is an area of expanding research interest. A staggering 40-60% of patients with COPD have cognitive impairments including deficits in executive functioning (e.g., decision making), processing speed, and memory. Intact cognition is critical for independently managing daily tasks (e.g., medication and money management). Since there are currently no treatments to fully reverse cognitive impairment once it is present, preventing and delaying onset is essential. Given the high prevalence of COPD, understanding how COPD confers an increased risk for cognitive impairment should be a top public health priority. There is an urgent need to identify potentially modifiable physiological characteristics of individuals with early COPD-related pathophysiology who are at risk of developing brain abnormalities. The earliest changes that occur in COPD are driven by an enhanced chronic inflammatory response that includes small airway disease in the lung and vascular abnormalities. COPD-related lung pathophysiology can be measured continuously and is separable from amount of smoking. These physiological changes are often present in individuals who do not meet traditional criteria for COPD diagnosis and have not yet manifested significant clinical symptoms. We propose that chronic smokers who are susceptible to COPD and show evidence of COPD-related lung pathophysiology on lung CT also experience vascular dysfunction (particularly central artery stiffness) that contributes to structural brain abnormalities and cognitive impairment. The proposed project will: 1) model the effects of novel physiological mechanisms on the brain in COPD, 2) focus on changes in brain structure and function early in the development of COPD by including smokers who have evidence of early COPD-related lung pathophysiology but do not meet traditional criteria for COPD, and 3) utilize advanced technology to assess the lung (lung CT) and brain (MRI). We will recruit participants with existing lung CT from ongoing NIH projects to complete pulmonary and vascular measures, cognitive assessment, and brain MRI. The project is highly multidisciplinary and leverages unique resources at the University of Iowa including the CTSA supported Institute for Clinical and Translational Science, the Translational Human Vascular Physiology Lab, the Iowa Neuroimaging Consortium, and the Iowa Comprehensive Lung Imaging Center.